We are interested in knowing how cells of a single organism can differentiate to form specific tissue types. We have chosen to address one aspect to the question by learning how one gene, the cut locus of Drosophila melanogaster, is expressed differently in different tissues of the fly. We have now cloned DNA sequences representing the entire gene, which encompasses 150 kb or more of DNA. A large number of mutants have been analyzed. We find that the deletion of sequences in the leftmost part of the gene cause phenotypic effects primarily in the legs, while deletion of or insertions into sequences slightly to the right cause effects primarily in the wings. Mutations in a third region 70 - 80Kb away at the rightmost end of the gene prevent expression in both legs and wings and cause lethality of the flies when homozygous. The availability of tissue specific mutants of a gene afford the opportunity to experiment to find out how the gene normally operates in tissue specific ways. We are currently studying the transcriptional activity of the cut locus and the DNA structure of normal and mutant alleles with the intention of finding out what causes the mutations and how the activity is altered. We now know that many of the cut mutants are insertions of retrovirus-like sequences into the cut locus DNA, and we are interested in understanding the affect of these sequences on gene activity. Some of these mutations are suppressible and will be useful in determining how a mutation caused by a retrovirus-like sequence can be suppressed.